Prevalence of Sleep Apnea in a Population of Adults with Type 2 Diabetes Mellitus

ObjectiveTo assess the prevalence of sleep apnea (SA) in adults with type 2 diabetes mellitus (T2DM) and examine whether demographics and comorbid factors were associated with SA in this population.MethodsThis study enrolled 330 consecutive adults with T2DM referred to a diabetes clinic, 279 of whom completed the study. Evaluation of the presence of SA was performed with use of a single-channel recording device that measures disordered breathing events from a nasal cannula airflow signal. The device was worn by the study participants in their home, after instruction in appropriate use by clinical staff at the diabetes center. The presence and severity of SA were determined by use of an apnea-hypopnea index (AHI), reflecting periods of diminished and absent breathing. Demographic and medical information data were collected to detect factors associated with SA in this study population. In addition, a time and cost analysis was conducted regarding the screening process for SA by clinical staff at the diabetes center.ResultsThe results show a high prevalence of SA in adults with T2DM, ranging from 48% (AHI level of ≥ 10 events/h) to 29% (AHI level of ≥ 20 events/h). At an AHI cutoff value of ≥ 15 events/h, the overall prevalence rate was 36% (49% in male and 21% in female participants). The following variables were associated with SA: age ≥ 62 years, male sex, body mass index ≥ 30 kg/m², snoring, and reports of stopping breathing during sleep. The time and cost analysis showed that the screening device involved minimal setup time, was simple to use, and was a cost-effective method to screen for SA.ConclusionSA is a common disorder associated with major morbid conditions, including hypertension, obesity, cardiovascular disease, and insulin resistance. Predisposing factors for SA and T2DM are similar. This study showed that SA has a high prevalence in adults with T2DM and identified factors that may be associated with its presence in this population. Assessment for SA can be easily performed in an outpatient setting with a portable recording device such as the one used in this study. Screening for SA should be considered in the T2DM population. (Endocr Pract. 2007;13:355-362)     

Saliva as a medium for aldosterone measurement in repeated sampling studies

BackgroundSaliva is a readily available biological fluid, making it convenient in diagnosis of diseases and in multi-sampling protocols. Several salivary steroids give a useful index of free plasma levels. Increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population has increased interest in the mineralocorticoid aldosterone.MethodsA biotinylated-aldosterone tracer and a commercially available antibody are used in a time-resolved fluorescence immunoassay (TR-FIA) to measure salivary aldosterone (SA). Saliva was collected in various multi-sampling protocols: Investigation of diurnal rhythm in healthy and PA patients, ACTH stimulation test and posture test in healthy subjects.ResultsMethod validation showed a sensitivity of 19 ng/L and intra-/inter-assay precision between 7.2–10.1% and 8.7–15.7%, respectively. SA correlated significantly (y = 0.2995x ± 0.01, r² = 0.60) to plasma aldosterone measured by a commercial radioimmunoassay. SA (median; 95%CI) was at 111 (95–127) ng/L in PA (n = 84) and 50 (44–56) ng/L in healthy subjects (n = 60). After change in posture, aldosterone increased in both, saliva (57 (47–63) ng/L to 95 (84–117) ng/L) and plasma (26 (26–41) ng/L to 135 (110–181) ng/L). Peak levels were reached after 1 h, and were higher in females than in males.ConclusionsSA correlates well to plasma aldosterone and mirrors responses during conditions of stress. SA is significantly higher in PA, and the diurnal rhythm seen in the healthy is blunted in PA. We additionally found gender-dependent differential responses to posture, with higher increases in females. Measurement of aldosterone in saliva presents a useful and convenient method for application in multi-sampling studies.     

Selecting proper combination of mpMRI sequences for prostate cancer classification using multi-input convolutional neuronal network

PurposeThis study aims to develop a deep-learning-based method to classify clinically significant (CS) and clinically insignificant (CiS) prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) automatically, and to select suitable mpMRI sequences for PCa classification in different anatomic zones.MethodsA multi-input selection network (MISN) is proposed for both PCa classification and the selection of the optimal combination of sequences for PCa classification in a specific zone. MISN is a multi-input/-output classification network consisting of nine branches to process nine input images from the mpMRI data. To improve classification accuracy and reduce model parameters, a pruning strategy is proposed to select a subset of the nine branches of MIST to form two more effective networks for the peripheral zone (PZ) PCa and transition zone (TZ) PCa, which are named as PZN and TZN, respectively. Besides, a new penalized cross-entropy loss function is adopted to train the networks to balance the classification sensitivity and specificity.ResultsThe proposed methods were evaluated on the PROSTATEx challenge dataset and achieved an area under the receiver operator characteristics curve of 0.95, which was much higher than currently published results and ranked first out of more than 1500 entries submitted to the challenge at the time of submission of this paper. For PZ-PCa and TZ-PCa classification, PZN and TZN achieved better performance than MISN.ConclusionsHigher performance can be achieved by selecting a suitable subset of the mpMRI sequences in PCa classification.     

Prostate cancer specific survival in the Prostate,Lung, Colorectal,and Ovarian (PLCO) Cancer Screening Trial

Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods: 76,693 men aged 55–74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan–Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results: There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51–0.68) for all PLCO cases, 0.66 (95% CI: 0.51–0.81) for Gleason 5–7 cases and 1.07 (95% CI: 0.87–1.3) for Gleason 8–10 cases. Conclusion: Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable.     

Increased risk of breast cancer in women with false-positive test: The role of misclassification

IntroductionStudies have shown that women with a false-positive result from mammography screening have an excess risk for breast cancer compared with women who only have negative results. We aimed to assess the excess risk of cancer after a false-positive result excluding cases of misclassification, i.e. women who were actually false-negatives instead of false-positives.MethodWe used data from the Copenhagen Mammography Screening Programme, Denmark. The study population was the 295 women, out of 4743 recalled women from a total of 58,003 participants, with a false-positive test during the screening period 1991–2005 and who later developed breast cancer. Cancers that developed in the same location as the finding that initially caused the recall was studied in-depth in order to establish whether there had been misclassification.ResultsSeventy-two cases were found to be misclassified. When the women with misclassified tests had been excluded, there was an excess risk of breast cancer of 27% (RR = 1.27, 95% confidence interval (CI), 1.11–1.46) among the women with a false-positive test compared to women with only negative tests. Women with a false-positive test determined at assessment had an excess risk of 27%, while false-positives determined at surgery had an excess risk of 30%.ConclusionsThe results indicate that the increased risk is not explained only by misclassification. The excess risk remains for false-positives determined at assessment as well as at surgery, which favours some biological susceptibility. Further research into the true excess risk of false positives is warranted.     

Associations between prior HPV4 vaccine doses and cervical cancer screening participation

BackgroundCervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination.MethodsUsing electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14⿿26 y vaccinated (n = 1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n = 1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression.ResultsScreening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR = 2.98 95% Confidence Interval (CI):2.45⿿3.61) and were more likely to screen than those receiving two (1 vs. 2, HR = 2.94 95% CI:2.09⿿4.14) or three doses (1 vs. 3, HR = 3.15 95% CI:2.21⿿4.48). Compared to unvaccinated women, women <21 y who completed 3-doses were 1.8-times more likely to screen at ⿥21 y, whereas vaccinated women ⿥21 y were more likely to screen regardless of number of doses (p < 0.0001).ConclusionsWomen who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.     

Circulating IL-6 concentrations and associated anthropometric and metabolic parameters in South Asian men and women in comparison to European whites

ObjectiveTo determine any ethnic differences in circulating interleukin (IL)-6 concentrations among SAs and Europeans, and to assess their relationship with body composition and insulin resistance measures.MethodsBody composition was assessed among 80 SA and European men and women using anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan. Oral glucose tolerance tests with insulin response were performed to assess insulin resistance measures. IL-6 levels were measured by high sensitivity ELISA.ResultsMedian IL-6 values were higher in SA compared with European women: 1.94 mg/l versus 1.51 mg/l, p = 0.041, but not so in men (1.56 mg/l versus 1.57 mg/l). Only measures of obesity, in particular percentage fat area (r = 0.6, p = 0.003), were positively correlated with IL-6 in SAs. Differences in body fat percentage (visceral and total) could explain up to 30% of the IL-6 difference between Asian and European women.ConclusionSA women have elevated circulating IL-6 levels, in part due to greater visceral and percent fat levels compared with European women. This observation may in part explain why Asians are at elevated cardiovascular disease risk. Future studies should address the effects of lifestyle factors (physical activity, diet) on plasma IL-6 concentrations in SA women.     

Childhood leukemia mortality and farming exposure in South Korea: A national population-based birth cohort study

ObjectivesThe aim of this study was to evaluate the relationship between leukemia mortality and exposure to farming among children in South Korea.MethodsA retrospective cohort study of South Korean children was conducted using data collected by the national birth register between 1995 and 2006; these data were then individually linked to death data. A cohort of 6,479,406 children was followed from birth until either their death or until December 31, 2006. For surrogate measures of pesticide exposure, we used residence at birth, paternal occupation, and month of conception from the birth certificate. Farming and pesticide exposure indexes by county were calculated using information derived from the 2000 agricultural census. Poisson regression analyses were used to calculate rate ratios (RRs) of childhood leukemia deaths according to indices of exposure to agricultural pesticides after adjustment for potential confounders.ResultsIn total 585 leukemia deaths were observed during the study period. Childhood leukemia mortality was significantly elevated in children born in rural areas (RR = 1.43, 95%CI 1.09–1.86) compared to those in metropolises, and in counties with both the highest farming index (RR = 1.33, 95%CI 1.04–1.69) and pesticide exposure index (RR = 1.30, 95%CI 1.02–1.66) compared to those in the reference group. However, exposure–response associations were significant only in relation to the farming index. When the analyses were limited to rural areas, the risk of death from leukemia among boys conceived between spring and fall increased over those conceived in winter.ConclusionsOur results show an increase in mortality from childhood leukemia in rural areas; however, further studies are warranted to investigate the environmental factors contributing to the excess mortality from childhood leukemia in rural areas.     

Liquid chromatography–tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid

BackgroundAnalysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography–tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated.MethodsThe method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2 → 87.0 (SA) and m/z 311.2 → 90.0 (¹³C₃-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients’ samples with known differences in SA metabolites like meningitis (n = 6), brain tumour (n = 2), leukaemia (n = 5), and Salla disease (n = 1).ResultsLimit of detection (LOD) was 0.54 μM for FSA and 0.45 μM for TSA. Intra- and inter-assay variation for FSA (21.8 μM) were 4.8% (n = 10) and 10.4% (n = 40) respectively. Intra- and inter-assay variation for TSA (35.6 μM) were 9.7% (n = 10) and 12.8% (n = 40) respectively. Tested patients showed values of TSA above established reference value.ConclusionThe validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses.     

Predictors of non-participation in cervical screening in Denmark

PurposeThe aims of this study were to identify demographic and socio-economic predictors of non-participation in cervical screening in Denmark, and to evaluate the influence of health care use on screening participation.MethodsA population based register study was undertaken using data from the Central Population Register, the national Patobank, and Statistics Denmark. The study included women aged 25–54 years on 1st of January 2002, living in Denmark during the next 5 years, and without a history of total hysterectomy, N = 1,052,447. Independent variables included age, civil status, nationality, level of education, and use of health care. Associations with non-participation in screening were determined with logistic regression.ResultsMain predictors of non-participation were limited or no contact with dental services (odds ratio (OR) = 2.36), general practitioners (OR = 1.75), and high age (OR = 1.98). Other important factors for non-participation were primary school education only (OR = 1.53), not being married (OR = 1.49), and foreign nationality (OR = 1.32).ConclusionA 2–1.5-fold difference in non-participation in cervical screening in Denmark was found across various population sub-groups. Increased screening compliance among women with primary school education only, and limited or no use of primary health care services in general could potentially diminish the current social inequalities in cervical cancer incidence, and thus decrease the overall high incidence of this disease in Denmark.     

Biochemical relapse free survival rate in patients with prostate cancer treated with external radiotherapy: outcomes obtained at the CMN Siglo XXI Hospital de Oncología,CMN 20 de Noviembre and Hospital General de México of the México City

AimBiochemical relapse-free survival (bRFS) rate is determined by a cohort of Mexican patients (n = 595) with prostate cancer who received treatment with external radiotherapy.BackgroundPatients with prostate cancer were collected from CMN Siglo XXI (IMSS), CMN 20 de Noviembre (ISSSTE), and Hospital General de México (HGM). For the IMSS, 173 patients that are treated with three-dimensional conformal radiation therapy (3D-CRT) and 250 with SBRT, for the ISSSTE 57 patients are treated with 3D-CRT and on the HGM 115 patients are managed with intensity modulated radiation therapy (IMRT). The percentage of patients by risk group is: low 11.1%, intermediate 35.1% and high 53.8%. The average follow-up is 39 months, and the Phoenix criterion was used to determine the bRFS.Materials and methodsThe Kaplan–Meier technique for the construction of the survival curves and, the Cox proportional hazards to model the cofactors.Results(a) The bRFS rates obtained are 95.9% for the SBRT (7 Gy fx, IMSS), 94.6% for the 3D-CRT (1.8 Gy fx, IMSS), 91.3% to the 3D-CRT (2.65 Gy fx, IMSS), 89.1% for the SBRT (7.25 Gy fx, IMSS), 88.7% for the IMRT (1.8 Gy fx, HGM) %, and 87.7% for the 3D-CRT (1.8 Gy fx, ISSSTE). (b) There is no statistically significant difference in the bRFS rates by fractionation scheme, c) Although the numerical difference in the bRFS rate per risk group is 95.5%, 93.8% and 89.1% for low, intermediate and high risk, respectively, these are not statistically significant.ConclusionsThe RT techniques for the treatment of PCa are statistically equivalent with respect to the bRFS rate. This paper confirms that the bRFS rates of Mexican PCa patients who were treated with conventional vs. hypofractionated schemes do not differ significantly.     

The use of spatial ecological modelling as a tool for improving the assessment of geographic range size of threatened species

We analysed endemic threatened tree and reptile species of Socotra Island (Yemen), characterised by different ecological requirements and spatial distribution, in order to evaluate the usefulness of spatial ecological modelling in the estimation of species extent of occurrence (EOO) and area of occupancy (AOO). Point occurrences for the entire species range were used to model their spatial distribution by Random Forest (RF) and Generalised Linear Model (GLM). For each species the suitability area (SA) was obtained by applying the 0% omission error criterion on the probability map, and compared or integrated with EOO and AOO area obtained by topological methods such as the minimum convex polygon (MCP), α-hull and 2 km × 2 km grid.RF showed a lower prediction error than GLM. Higher accuracy was achieved for species with higher number of occurrences and narrower ecological niche. SA was always greater than AOO measured with the 2 km × 2 km grid method. SA was greater than EOO, measured by both MCP and α-hull methods, for species with localised distribution, while it was smaller for widely distributed species. EOO-α-hull area was equal or smaller than that calculated by MCP depending on the spatial distribution of species. AOO measured considering the SA within the EOO-MCP was greater than that measured using the standard 2 km × 2 km grid. Conversely, AOO calculated considering the suitable area within the EOO-α-hull showed variable results, being smaller or greater than the 2 km × 2 km grid AOO depending on the ecological niche and spatial distribution of species. According to our results, SEM does not provide an effective alternative to topological methods for the estimate of EOO and AOO. However, it may be considered a useful tool to estimate AOO within the boundaries of EOO measured by the α-hull method, because it reduces some potential sources of inconsistency and bias.     

Evaluación de la realización del cribado del pie diabético en Atención Primaria

AimTo ascertain whether patients with type 2 diabetes are screened for diabetic foot, and to analyze the factors related to patients and centers associated to performance of such screening.Material and methodsA multicenter, epidemiological, cross-sectional study was conducted. The clinical records of 443 patients with type 2 diabetes monitored at Primary Care for at least 12 months were reviewed. Demographic and healthcare variables and characteristics of the primary care center were recorded.ResultsIn the previous year, 51.2% of patients had been trained on foot self-care, 56.4% had undergone foot inspection, 39.5% had been examined with a monofilament, and palpation of peripheral pulses and measurement of the ankle-brachial index were performed in 45.8 and 10.1% of patients, respectively. Diabetic foot screening (inspection, monofilament testing, and palpation of peripheral pulses) was performed in 37% of study patients. Ulcer risk stratification was done in 12.4% of patients. A significant association was found between diabetic foot screening and presence of foot deformities (P < .001), history of neuropathy (P = .005), and history of peripheral artery disease (P < .05). Screening was also associated to some characteristics of the center, such as reception of information about goal achievement (P < .001) and economic incentives for goal attainment (P < .001).ConclusionsCompliance with diabetic foot screening and ulcer risk stratification in patients with type 2 diabetes in Primary Care was poor.     

Effect of modified MRS medium on production and purification of antimicrobial peptide ST4SA produced by Enterococcus mundtii

Highest antimicrobial activity of peptide ST4SA (51,200 AU/mL) was recorded after 14 h of growth in MRS broth with optimal production at pH 6.0 or 6.5. Growth of strain ST4SA in the presence of tryptone, yeast extract, or a combination of the two, yielded 102,400 AU/mL. An increase in production of peptide ST4SA to 102,400 AU/mL was recorded in the presence of 20.0 g/L fructose, but decreased to 25,600 AU/mL in the presence of lactose (20.0 g/L) or mannose (20.0 g/L) as sole carbon source. Lower activity (25,600 AU/mL) was recorded when 2.0 g/L K₂HPO₄ was replaced by 2.0 g/L KH₂PO₄ in MRS broth. An increase of K₂HPO₄ to 10.0 g/L and 20.0 g/L resulted in higher activity (102,400 AU/mL). Addition of glycerol to MRS broth had a negative effect on peptide ST4SA production. Production of peptide ST4SA required the presence of magnesium sulphate, manganese sulphate and 5.0 g/L sodium acetate. Exclusion of tri-ammonium citrate from the medium resulted in reduction of activity to 3,200 AU/mL. Maximum activity (102,400 AU/mL) was recorded in MRS supplemented with 1.0 ppm Vit. C, DL-6,8-thioctic acid or thiamine, respectively. Growth of Listeria ivanovii susbp. ivanovii ATCC 19119 in the presence of peptide ST4SA (12,800 AU/mL) resulted in 99% cell lysis after 18 h. Improved production of peptide ST4SA was recorded in MRS broth (Biolab) pre-treated with Amberlite XAD-1180. Precipitation with ammonium sulphate, followed by gel filtration chromatography, yielded the highest level of peptide ST4SA. This paper describes the partially deproteination of growth medium to facilitate peptide ST4SA purification.     

Fermentation process for continuous production of succinic acid in a fibrous bed bioreactor

Succinic acid (SA) was produced from Actinobacillus succinogenes with high cell density by continuous fermentation using fibrous bed bioreactor (FBB). The effects of feeding glucose concentration, dilution rate, and pH on continuous production of SA were examined to achieve an efficient and economical bioprocess. The optimum feeding glucose concentration, dilution rate, and pH were 80 g/L, 0.05 1/h, and 6.0–6.5, respectively. A SA concentration of 55.3 ± 0.8 g/L, productivity of 2.77 ± 0.04 g/L/h, and yield of 0.8 ± 0.02 g/g were obtained, and the continuous fermentation exhibited long-term stability for as long as 18 days (440 h) with no obvious fluctuations in both SA and biomass levels. The Jerusalimsky equation for the specific rate of SA production presented the inhibition phenomenon of the product, demonstrating that 60 g/L SA might be a critical concentration in this continuous FBB system. The results obtained could be beneficial for future fermentor designs and improvements in SA production.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

Human Papillomavirus (HPV) 16 E6 seropositivity is elevated in subjects with oral HPV16 infection

IntroductionHuman Papillomavirus (HPV) 16 E6 serum antibodies are common in people with HPV-related oropharyngeal cancers (HPV-OPC), but not the general population. We explored HPV16 seroprevalence in people with and without oral HPV16 infection, the cause of HPV-OPC.MethodsOral rinse samples were collected semiannually and tested for 36 types of HPV DNA by PCR. HPV16 E6 serum antibodies were tested at the visit of first oral HPV detection in participants with prevalent (n = 54), or incident (n = 39) oral HPV16 DNA; or at baseline in matched participants with no oral HPV16 DNA (n = 155) using multiplex serology assay. Predictors of seropositivity were examined using logistic regression.ResultsHPV16 E6 seropositivity (7.5% vs 0.7%; p = 0.005) but not seropositivity to the other HPV16 antigens, was significantly more common in those with than without oral HPV16 infection. There were only 8 HPV16 E6 seropositive participants, but oral HPV16 DNA remained a strong predictor of E6 seropositivity after adjustment for other risk factors (aOR = 14.6 95%CI, 1.7–122.5). Seroprevalence was similar in those with prevalent (7.4%; 4/54), and incident (7.7%; 3/39) oral HPV16 infection (p = 1.00). E6 seroprevalence was associated with reduced oral HPV16 clearance, but was not statistically significant (HR = 0.65 95% CI, 0.16–2.70).Seropositive participants were primarily male (87.5%), HIV-positive (75.0%; median CD4 cell-count of 840) and had oral HPV16 DNA (87.5%). History of an HPV-related cancer (0/8) or HPV-related anogenital dysplasia (1/8) was rare, and 4 participants had recent screening showing no anogenital dysplasia.DiscussionHPV16 E6 seropositivity was higher among people with than without oral HPV16 infection, despite no known anogenital disease in these participants.     

The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level <2.5 ng/ml

IntroductionIt is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings.MethodsBetween 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N = 1710) or palpable (T2–T4, N = 7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA < 2.5 ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM.ResultsAfter median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR = 3.52; 95% CI: 1.25–9.89; P = .017) in men with T1c, Gleason score 7–10 PC, but decreased PCSM risk (AHR = 0.66; 95% CI: 0.52–0.83; P < .001) for men with T2–T4 PC and any Gleason score.DiscussionFor men with diagnostic PSA level <2.5 ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA.     

Achievement of therapeutic targets in Mexican patients with diabetes mellitus

Background and aimComplications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus.MethodsWe analyzed data from 2642 Mexican patients with type 1 (T1D, n = 203, 7.7%) and type 2 diabetes (T2D, n = 2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study.ResultsOf T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) < 7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c < 7%, blood pressure < 130/80 mmHg and low-density lipoprotein cholesterol < 100 mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c < 7% was associated with a reduced number of microvascular but not with less macrovascular complications.ConclusionA great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease.